Abstract
In 1930, a German physician wrote a paper in which he most strongly suggested that smoking of cigarettes is a cause of lung cancer (1). In the same year, Mertens (2) published the results of a study in which he had exposed individual mice to cigarette smoke. He used a compressible rubber bulb to force cigarette smoke into a glass desiccator. Exposures were from 1-4 h daily, for up to 15 mo. Upon histological examination, he observed inflammatory changes in the lungs, although he was quick to point out that large areas of the lungs showed no pathological alterations. Neoplastic lung lesions were found in two animals. In one mouse, multiple small nodules, classified as adenocarcinomas, were considered to have been pre-existing. The second animal showed several small nodules and, in addition, one large adenocarcinoma, mm in diameter, originating in a bronchus and invading the adjacent parenchyma. The author summarized his findings by stating that he had found one bronchial cancer, but that it was doubtful whether it had been caused by tobacco smoke.
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Lickint, F. (1930) Tabak und Tabakrauch als aetiologischer Faktor des Carcinoms. Zeitschrift fuer Krebsforschung 30, 349–365.
Mertens, V. E. (1930) Zigarettenrauch eine Ursache des Lungenkrebses? (Eine Anregung). Zeitschrift fuer Krebsforschung 32, 82–91.
Mohr, U. and Reznik, G. (1978) Tobacco Carcinogenesis, in Pathogenesis and Therapy of Lung Cancer (Harris, C. C., ed.), Marcel Dekker, Inc., New York, pp. 263–368.
International Agency for Research on Cancer (IARC) (1986) Biological Data Relevant to the Evaluation of Carcinogenic Risk to Humans. 1. Carcinogenicity Studies in Animals, in IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Tobacco Smoking Vol. 38 (WHO IARC, ed.), IARC, Lyon, pp. 127–139.
Henry, C. J. and Kouri, R. E. (1984) Chronic Exposure of Mice to Cigartte Smoke. Final Report, The Council for Tobacco Research-USA, Inc. Contract CTR-030, “Smoke Inhalation in Mice.” Field, Rich & Associates, New York.
Henry, C. J. and Kouri, R. E. (1986) Chronic inhalation studies in mice. II. Effects of long-term exposure to 2R1 cigarette smoke on (C57BL/Cum × C3H/AnfCum)F1 mice. J. Natl. Cancer Inst. 77, 203–212.
Leuchtenberger, C. and Leuchtenberger, R. (1970) Effects of chronic inhalation of whole fresh cigarette smoke and of its gas phase on pulmonary tumorigenesis in Snell’ s mice, in Morphology of Experimental Respiratory Carcinogenesis. (Nettesheim, P., Hanna, M. G., Jr., and Deatherage, J. W., Jr., eds.) Proceedings of a Biology Division, Oak Ridge National Laboratory, Conference held in Gatlinburg, Tennessee, May 13-16, 1970. US Atomic Energy Commission, Division of Technical Information, Washington, DC, pp. 329–346.
Leuchtenberger, C. and Leuchtenberger, R. (1974) Differential response of Snell’ s and C57 black mice to chronic inhalation of cigarette smoke. Pulmonary carcinogenesis and vascular alterations in lung and heart. Oncology 29, 122–138.
Harris, R. J., Negroni, G., Ludgate, S., Pick, C. R., Chesterman, F. C., and Maidment, B. J. (1974) The incidence of lung tumours in c57bl mice exposed to cigarette smoke: air mixtures for prolonged periods. Int. J. Cancer 14, 130–136.
Finch, G. L., Nikula, K. J., Barr, E. B., Bechtold, W. E., Chen, B. T., Griffith, W. C., et al. (1995) Lung tumor synergism between 239PuO2 and cigarette smoke inhaled by Fisher 344 rats. Toxicologist 15, 47 (Abstract).
Finch, G. L., Nikula, K. J., Belinsky, S. A., Barr, E. B., Stoner, G. D., and Lechner, J. F. (1996) Failure of cigarette smoke to induce or promote lung cancer in the A/J mouse. Cancer Lett. 99, 161–167.
Coggins, C. R. E. (1998) A review of the chronic inhalation studies with mainstream cigarette smoke in rats and mice. Toxicol. Pathol. 26, 307–314.
Hecht, S. S. (1999) Tobacco smoke carcinogens and lung cancer. J. Natl. Cancer Inst. 91, 1194–1210.
Binns, R., Lugton, W. G., and Dyas, B. J. (1978) The effect of exposure conditions on cigarette smoke deposition in the respiratory system of male rats, in Clinical Toxicology (Duncan, W. A. and Leonard, B. J., eds.), Excerpta Medica, Amsterdam, pp. 267–269.
Binns, R., Lugton, W. G., Wilton, L. V., and Dyas, B. J. (1978) Inhalation toxicity studies on cigarette smoke. V. Deposition of smoke particles in the respiratory system of rats under various exposure conditions. Toxicology 9, 87–102.
Witschi, H. P., Oreffo, V. I. C., and Pinkerton, K. E. (1995) Six month exposure of strain A/J mice to cigarette sidestream smoke: cell kinetics and lung tumor data. Fundam. Appl. Toxicol. 26, 32–40.
Witschi, H. P., Espiritu, I., Peake, J. L., Wu, K., Maronpot, R. R., and Pinkerton, K. E. (1997) The carcinogenicity of environmental tobacco smoke. Carcinogenesis 18, 575–586.
Witschi, H. P., Espiritu, I., Maronpot, R. R., Pinkerton, K. E., and Jones, A. D. (1997) The carcinogenic potential of the gas phase of environmental tobacco smoke. Carcinogenesis 18, 2035–2042.
Mauderly, J. L., Bechtold, W. E., Bond, J. A., Brooks, A. L., Chen, B. T., Cuddihy, R. G., Harkema, J. R., Henderson, R. F., Johnson, N. F., and Rithidech, K. (1989) Comparison of 3 methods of exposing rats to cigarette smoke. Exp. Pathol. 37, 194–197.
National Cancer Institute (1999) Health Effects of Exposure to Environmental Tobacco Smoke: The Report of the California Environmental Protection Agency. Smoking and Tobacco Control Monograph No. 10. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, NIH Pub. No. 99-4645, Bethesda MD.
Shimkin, M. B. and Stoner, G. D. (1975) Lung tumors in mice: application to carcinogenesis bioassay. Adv. Cancer Res. 21, 1–58.
Lorenz, E., Stewart, H. L., Daniel, J. H., and Warren, S. (1943) The effects of breathing tobacco smoke on strain A mice. Cancer Res. 3, 123. (Abstract.)
Essenberg, J. M. (1952) Cigarette smoke and the incidence of primary neoplasm of the lung in the albino mouse. Science 116, 561–562.
Essenberg, J. M., Horowitz, M., and Gaffney, E. (1955). The incidence of lung tumors in albino mice exposed to the smoke from cigarettes low in nicotine content. West. J. Surg. Obstet. Gynecol. 63, 265–267.
Essenberg, J. M. (1957) Further study of tumor formation in the lungs of the albino mice. West. J. Surg. Obstet. Gynecol. 65, 161–163.
Adkins, B. J., Van Stee, E. W., Simmons, J. E., and Eustis, S. L. (1986) Oncogenic response of strain A/J mice to inhaled chemicals. J. Toxicol. Environ. Health 17, 311–322.
Pepelko, W. E. and Peirano, W. B. (1983) Health effects of exposure to Diesel exhaust emissions. J. Am. Coll. Toxicol. 2, 253–306.
Leong, B. K., MacFarland, H. N., and Reese, W. H.,Jr. (1971) Induction of lung adenomas by chronic inhalation of bis (chloromethyl) ether. Arch. Environ. Health 22, 663–666.
Witschi, H., Espiritu, I., Pinkerton, K. E., Murphy, K., and Maronpot, R. (1999) Ozone Carcinogenesis Revisited. Toxicol. Sci. 52, 162–167.
Boorman, G. A., Sills, R. C., Grumbein, S., Hailey, R., Miller, R. A., and Herbert, R. A. (1995) Long-term toxicity studies of ozone in F344/N rats and B6C3F1 mice. Toxicol. Lett. 82–83, 301–306.
Stoner, G. D. and Shimkin, M. B. (1985) Lung tumors in strain A mice as a bioassay for carcinogenicity, in Handbook of Carcinogen Testing (Milman, H. and Weisburger, E. K., eds.), Noyes Publications, Park Ridge, NJ, pp. 179–214.
Hammond, E. C. (1966) Smoking in relation to the death rates of one million men and women. Natl. Cancer Inst. Monogr. 19, 127–204.
Wynder, E. L. and Stellman, S. D. (1977) Comparative epidemiology of tobacco-related cancers. Cancer Res. 37, 4608–4622.
Postmus, P. E. (1998) Epidemiology of lung cancer, in Fishman’ s Pulmonary Diseases and Disorders (Fishman, A. P., Elias, J. A., Fishman, J. A., Grippi, M. A., Kaiser, L. R., and Senior, R. M., eds.), McGraw-Hill, New York, pp. 1707–1717.
Witschi, H., Espiritu, I., and Uyeminami, D. (1999) Chemoprevention of tobacco smoke-induced lung tumors in A/J strain mice with dietary myo-inositol and dexamethasone. Carcinogenesis 20, 1375–1378.
Witschi, H., Uyeminami, D., Moran, D., and Espiritu, I. (2000) Chemoprevention of tobacco-smoke lung carcinogenesis in mice after cessation of smoke exposure. Carcinogenesis 21, 977–982.
Teague, S. V., Pinkerton, K. E., Goldsmith, M., Gebremichael, A., Chang, S., Jenkins, R. A., and Moneyhun, J. H. (1994) Sidestream cigarette smoke generation and exposure system for environmental tobacco smoke studies. Inhal. Toxicol. 6, 79–93.
Wong, B. A. (1999) Inhalation systems design, methods and operation, in Toxicology of the Lung (Gardner, D. E., Crapo, J. D., and McClellan, R. O., eds.), Taylor & Francis, Philadelphia, PA, pp. 1–53.
Hext, P. M. (1999) Inhalation Toxicology, in General and Applied Toxicology (Ballantyne, B., Marrs, T. C., and Syversen, T., eds.), Grove’ s Dictionaries, Inc., New York, pp. 587–602.
Kennnedy, G. L. and Valentine, R. (1994) Inhalation Toxicology, in Principles and Methods of Toxicology (Hayes, A. W., ed.), Raven Press, New York, pp. 805–838.
Dontenwill, W. (1970) Experimental investigations on the effect of cigarette smoke inhalation on small laboratory animals, in Morphology of Experimental Respiratory Carcinogenesis (Nettesheim, P., Hanna, M. G., Jr., and Deatherage, J. W., Jr., eds.), Proceedings of a Biology Division, Oak Ridge National Laboratory, conference held in Gatlinburg, Tennessee, May 13–16, 1970. U.S. Atomic Energy Commission, Division of Technical Journals, Washington, DC, pp. 389–412.
Baumgartner, H. and Coggins, C. R. (1980) Description of a continuous-smoking inhalation machine for exposing small animals to tobacco smoke. Beitr. Tabakforsch. Int. 10, 169–174.
Guerin, M. R., Jenkins, R. A., and Tomkins, B. A. (1992) The Chemistry of Environmental Tobacco Smoke: Composition and Measurement. Indoor Air Research Series. Lewis Publishers, Boca Raton, FL.
Ayres, P. H., Mosberg, A. T., and Coggins, C. R. (1994) Design, construction, and evaluation of an inhalation system for exposing experimental animals to environmental tobacco smoke. Am. Ind. Hyg. Assoc. J. 55, 806–810.
Coggins, C. R., Ayres, P. H., Mosberg, A. T., Ogden, M. W., Sagartz, J. W., and Hayes, A. W. (1992) Fourteen-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette. I. Inhalation toxicology and histopathology. Fundam. Appl. Toxicol. 19, 133–140.
Lee, C. K., Brown, B. G., Reed, E. A., Coggins, C. R., Doolittle, D. J., and Hayes, A. W. (1993) Ninety-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette: DNA adducts and alveolar macrophage cytogenetics. Fundam. Appl. Toxicol. 20, 393–401.
Haussmann, H. J., Anskeit, E., Becker, D., Kuhl, P., Stinn, W., Teredesai, A., et al. (1998) Comparison of fresh and room-aged cigarette sidestream smoke in a subchronic inhalation study on rats. Toxicol. Sci. 41, 100–116.
Haussmann, H. J., Gerstenberg, B., Goecke, W., Kuhl, P., Schepers, G., Stabbert, R., et al. (1998) 12-Month inhalation study on room-aged cigarette sidestream smoke in rats. Inhal. Toxicol. 10, 663–697.
Griffith, R. B. (1984) A simple machine for smoke analytical studies and total particulate matter collection for biological studies. Toxicology 33, 33–41.
Griffith, R. B. and Hancock, R. (1985) Simultaneous mainstream-sidestream smoke exposure systems I. Equipment and procedures. Toxicology 34, 123–138.
Griffith, R. B. and Standafer, S. (1985) Simultaneous mainstream-sidestream smoke exposure systems II. The rat exposure system. Toxicology 35, 13–24.
Witschi, H. P. (1981) Enhancement of tumor formation in mouse lung by dietary butylated hydroxytoluene. Toxicology 21, 95–104.
Maronpot, R. R., Shimkin, M. B., Witschi, H. P., Smith, L. H., and Cline, J. M. (1986) Strain A mouse pulmonary tumor test results for chemicals previously tested in the National Cancer Institute carcinogenicity tests. J. Natl. Cancer Inst. 76, 1101–1112.
Maronpot, R. R. (1991) Correlation of data from the strain A mouse bioassay with long-term bioassays. Exp. Lung Res. 17, 425–431.
Witschi, H., Espiritu, I., Yu, M., and Willits, N. H. (1998) The effects of phenethyl isothiocyanate, N-acetylcysteine and green tea on tobacco smoke-induced lung tumors in strain A/J mice. Carcinogenesis 19, 1789–1794.
Witschi, H. (2000) Successful and not so successful chemoprevention of tobacco smoke-induced lung tumors. Exp. Lung Res. 26, 743–756.
John, L. C. H. (2001) Assessment of murine lung tumour development: a comparison of two techniques. Br. J. Biomed. Sciences 58, 159–163.
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Witschi, H. (2003). Induction of Lung Cancer by Passive Smoking in an Animal Model System. In: Driscoll, B. (eds) Lung Cancer. Methods in Molecular Medicine™, vol 74. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-323-2:441
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DOI: https://doi.org/10.1385/1-59259-323-2:441
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